8 results on '"Jack Wadden"'
Search Results
2. Liquid biopsy in pediatric brain tumors
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Arushi Tripathy, Vishal John, Jack Wadden, Seongbae Kong, Sana Sharba, and Carl Koschmann
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liquid biopsy ,pediatric ,brain tumor ,cell-free tumor DNA (cf-tDNA) ,cerebrospinal fluid (CSF) ,plasma ,Genetics ,QH426-470 - Abstract
Malignant primary brain tumors are the most common cancer in children aged 0–14 years, and are the most common cause of death among pediatric cancer patients. Compared to other cancers, pediatric brain tumors have been difficult to diagnose and study given the high risk of intracranial biopsy penetrating through vital midline structures, where the majority of pediatric brain tumors originate (Ostrom et al., 2015). Furthermore, the vast majority of these tumors recur. With limitations in the ability to monitor using clinical and radiographic methods alone, minimally invasive methods such as liquid biopsy will be crucial to our understanding and treatment. Liquid biopsy of blood, urine, and cerebrospinal fluid (CSF) can be used to sample cfDNA, ctDNA, RNA, extracellular vesicles, and tumor-associated proteins. In the past year, four seminal papers have made significant advances in the use of liquid biopsy in pediatric brain tumor patients (Liu et al., 2021; Cantor et al., 2022; Miller et al., 2022; Pagès et al., 2022). In this review, we integrate the results of these studies and others to discuss how the newest technologies in liquid biopsy are being developed for molecular diagnosis and treatment response in pediatric brain tumors.
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- 2023
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3. SquiggleNet: real-time, direct classification of nanopore signals
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Yuwei Bao, Jack Wadden, John R. Erb-Downward, Piyush Ranjan, Weichen Zhou, Torrin L. McDonald, Ryan E. Mills, Alan P. Boyle, Robert P. Dickson, David Blaauw, and Joshua D. Welch
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Deep learning ,Read-until ,Oxford Nanopore ,Raw signal ,Real-time ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Abstract We present SquiggleNet, the first deep-learning model that can classify nanopore reads directly from their electrical signals. SquiggleNet operates faster than DNA passes through the pore, allowing real-time classification and read ejection. Using 1 s of sequencing data, the classifier achieves significantly higher accuracy than base calling followed by sequence alignment. Our approach is also faster and requires an order of magnitude less memory than alignment-based approaches. SquiggleNet distinguished human from bacterial DNA with over 90% accuracy, generalized to unseen bacterial species in a human respiratory meta genome sample, and accurately classified sequences containing human long interspersed repeat elements.
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- 2021
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4. Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy
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Jack Wadden, Karthik Ravi, Vishal John, Clarissa May Babila, and Carl Koschmann
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liquid biopsy ,glioma ,immunotherapy ,cell-free tumor DNA (cf-tDNA) ,Csf ,plasma ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Gliomas are tumors derived from mutations in glial brain cells. Gliomas cause significant morbidity and mortality and development of precision diagnostics and novel targeted immunotherapies are critically important. Radiographic imaging is the most common technique to diagnose and track response to treatment, but is an imperfect tool. Imaging does not provide molecular information, which is becoming critically important for identifying targeted immunotherapies and monitoring tumor evolution. Furthermore, immunotherapy induced inflammation can masquerade as tumor progression in images (pseudoprogression) and confound clinical decision making. More recently, circulating cell free tumor DNA (cf-tDNA) has been investigated as a promising biomarker for minimally invasive glioma diagnosis and disease monitoring. cf-tDNA is shed by gliomas into surrounding biofluids (e.g. cerebrospinal fluid and plasma) and, if precisely quantified, might provide a quantitative measure of tumor burden to help resolve pseudoprogression. cf-tDNA can also identify tumor genetic mutations to help guide targeted therapies. However, due to low concentrations of cf-tDNA, recovery and analysis remains challenging. Plasma cf-tDNA typically represents
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- 2022
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5. Accelerating Maximal-Exact-Match Seeding with Enumerated Radix Trees
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Kush Goliya, Satish Narayanasamy, David Blaauw, Reetuparna Das, Jack Wadden, Nathan Ozog, Xiao Wu, and Arun Subramaniyan
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Computer science ,Radix tree ,Genome sequence analysis ,Seeding ,Human genome ,Parallel computing ,Data structure ,Genome ,Bottleneck - Abstract
MotivationRead alignment is a time-consuming step in genome sequence analysis. In the read alignment software BWA-MEM and the recently published faster version BWA-MEM2, the seeding step is a major bottleneck, for instance, contributing 38% to the overall execution time in BWA-MEM2 when aligning single-end whole human genome reads from the Platinum Genomes dataset. This is because both BWA-MEM and BWA-MEM2 use a compressed index structure called the FMD-Index, which results in high memory bandwidth requirements for seeding, primarily due to its character-by-character processing of reads.ResultsWe propose a memory bandwidth-aware data structure for maximal-exact-match seeding called Enumerated Radix Tree (ERT). ERT trades off memory capacity to improve seeding performance (∼60 GB index for human genome). Together with optimizations to the seeding algorithm and mate-rescue step, ERT when integrated into BWA-MEM2 speeds up overall read alignment by 1.28× and provides up to 2.1× higher seeding performance while guaranteeing identical output to the original software. Furthermore, we prototype an FPGA implementation of ERT on Amazon EC2 F1 cloud and observe 1.6× higher seeding throughput over a 48-thread optimized CPU-ERT implementation.Availability and implementationhttps://github.com/arun-sub/bwa-mem2Contactarunsub@umich.edu, reetudas@umich.edu
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- 2020
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6. EPCT-03. SERIAL PLASMA AND CSF CELL-FREE TUMOR DNA (CF-TDNA) TRACKING IN DIFFUSE MIDLINE GLIOMA PATIENTS UNDERGOING TREATMENT WITH ONC201
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Ian Wolfe, Ramya Ravindran, Rajen Mody, Carl Koschmann, Joshua E. Allen, Hugh J. L. Garton, Sunjong Ji, Sabine Mueller, Andrea Franson, Evan Cantor, Abed Rhaman Kawakibi, Partricia Robertson, Clarissa May Babilla, Soumen Khatua, Rodrigo Cartaxo, Johanna Ramos, Nicholas A Vitanza, Alyssa Paul, Marcia Leonard, Sharon Gardner, Rohinton S. Tarapore, Yazmin Odia, Chase Thomas, Amy K. Bruzek, Kyle Wierzbicki, Jack Wadden, Viveka Nand Yadav, and Cassie Kline
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Cancer Research ,Bevacizumab ,medicine.diagnostic_test ,business.industry ,Lumbar puncture ,Radiography ,Magnetic resonance imaging ,medicine.disease ,Spinal cord ,Translational/Early Phase Clinical Trials ,medicine.anatomical_structure ,Text mining ,Oncology ,Glioma ,Etiology ,Medicine ,AcademicSubjects/MED00300 ,AcademicSubjects/MED00310 ,Neurology (clinical) ,business ,Nuclear medicine ,medicine.drug - Abstract
Diffuse midline glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma ({"type":"clinical-trial","attrs":{"text":"NCT03416530","term_id":"NCT03416530"}}NCT03416530). Patients enrolled on Arm D of the trial (n=24) underwent serial lumbar puncture (baseline, 2, 6 months) for cell-free tumor DNA (cf-tDNA) analysis at time of MRI. Additionally, patients on all arms of the trial at the University of Michigan underwent serial plasma collection. CSF collection was feasible in this cohort, with no procedural complications. We collected 96 plasma samples and 53 CSF samples from 29 patients, including those with H3F3A (H3.3) (n=13), HIST13HB (H3.1) (n= 4), and unknown H3 status/not biopsied (n=12) [range of 0–8 CSF samples and 0–10 plasma samples]. We performed digital droplet polymerase chain reaction (ddPCR) analysis and/or amplicon-based electronic sequencing (Oxford Nanopore) of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Preliminary analysis of samples demonstrates a correlation between changes in tumor size and H3K27M cf-tDNA VAF, when removing samples with concurrent bevacizumab. In multiple cases, early reduction in CSF cf-tDNA predicts long-term clinical response (>1 year) to ONC201, and does not increase in cases of later-defined pseudo-progression (radiation necrosis). For example, a now 9-year old patient with thalamic H3K27M-mutant DMG underwent treatment with ONC201 after initial radiation and developed increase in tumor size at 4 months post-radiation (124% baseline) of unclear etiology at the time. Meanwhile, her ddPCR declined from baseline 6.76% VAF to
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- 2021
7. DIPG-08. ELECTRONIC SEQUENCING PROVIDES OPTIMIZED QUANTIFICATION OF SERIAL, MULTI-GENE MOLECULAR RESPONSE IN THE CSF OF CHILDREN WITH HIGH-GRADE GLIOMA
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Karin M. Muraszko, Ian Wolfe, Evan Cantor, Hugh J. L. Garton, Karthik Ravi, Ashwath Muruganand, Cormac O. Maher, Patrica Robertson, Leo Tunkle, Carl Koschmann, Tingting Qin, Rajen Mody, Stefanie Stallard, Andrea Franson, Clarissa Babila, Kyle Wierzbicki, Amy K. Bruzek, and Jack Wadden
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Cancer Research ,Oncology ,Molecular Response ,Diffuse Midline Glioma/DIPG ,Cancer research ,AcademicSubjects/MED00300 ,AcademicSubjects/MED00310 ,Neurology (clinical) ,Biology ,Multi gene ,High-Grade Glioma - Abstract
BACKGROUND For pediatric high-grade glioma (pHGG), non-invasive methods for diagnosis and surveillance are needed. Tumors release DNA (tDNA) into cerebrospinal fluid (CSF), allowing for detection of tumor-associated mutations by CSF sampling. We hypothesized that direct, electronic analysis of tDNA with a novel, hand-held platform (Oxford Nanopore MinION) could quantify patient-specific CSF tDNA variant allele fraction (VAF) with improved speed and limit of detection compared to established methods. METHODS We integrated required multi-timepoint (0, 2, and 6 months) correlate lumbar punctures (LP) in two ongoing pHGG clinical trials. Using Nanopore technology, we performed amplicon-based PCR on CSF tDNA for recurrent mutations from patient samples (n=19) and normal controls. VAF were determined via MinKNOW, Guppy, MiniMap2, and Integrated Genome Browser. RESULTS Nanopore CSF tDNA demonstrated improved sensitivity (91%) when compare to NGS sequencing (50%). Nanopore analysis of serially diluted CSF sample demonstrated significantly lower limit of detection (attomolar) than typical NGS sample requirement (nanomolar). H3K27M mutation was reliably detected with 1,000x depth sequencing, which was achieved in less than 15 minutes of sequencing after amplification. Multiplexed Nanopore analysis of H3F3A and HIST1H3B was employed when H3 status was unknown. Serial CSF tDNA analysis confirmed multi-gene (H3F3A K27M, PIK3CA, and TP53) molecular remission in a 17-year-old with thalamic diffuse midline glioma that correlated with sustained clinical response to ONC201 (14 months and ongoing). CONCLUSIONS Use of a hand-held, electronic DNA analysis platform allows quantification of multi-gene molecular response with improved speed and limit of detection in the CSF of children with high-grade glioma.
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- 2020
8. A compliant mechanism for inspecting extremely confined spaces.
- Author
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David Mascareñas, Fernando Moreu, Precious Cantu, Daniel Shields, Jack Wadden, Mohamed El Hadedy, and Charles Farrar
- Abstract
We present a novel, compliant mechanism that provides the capability to navigate extremely confined spaces for the purpose of infrastructure inspection. Extremely confined spaces are commonly encountered during infrastructure inspection. Examples of such spaces can include pipes, conduits, and ventilation ducts. Often these infrastructure features go uninspected simply because there is no viable way to access their interior. In addition, it is not uncommon for extremely confined spaces to possess a maze-like architecture that must be selectively navigated in order to properly perform an inspection. Efforts by the imaging sensor community have resulted in the development of imaging sensors on the millimeter length scale. Due to their compact size, they are able to inspect many extremely confined spaces of interest, however, the means to deliver these sensors to the proper location to obtain the desired images are lacking. To address this problem, we draw inspiration from the field of endoscopic surgery. Specifically we consider the work that has already been done to create long flexible needles that are capable of being steered through the human body. These devices are typically referred to as ‘steerable needles.’ Steerable needle technology is not directly applicable to the problem of navigating maze-like arrangements of extremely confined spaces, but it does provide guidance on how this problem should be approached. Specifically, the super-elastic nitinol tubing material that allows steerable needles to operate is also appropriate for the problem of navigating maze-like arrangements of extremely confined spaces. Furthermore, the portion of the mechanism that enters the extremely confined space is completely mechanical in nature. The mechanical nature of the device is an advantage when the extremely confined space features environmental hazards such as radiation that could degrade an electromechanically operated mechanism. Here, we present a compliant mechanism developed to navigate maze-like arrangements of extremely confined spaces. The mechanism is shown to be able to selectively navigate past three 90° bends. The ability to selectively navigate extremely confined spaces opens up new possibilities to use emerging miniature imaging technology for infrastructure inspection. [ABSTRACT FROM AUTHOR]
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- 2017
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